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Corrinoid (vitamin B12-like) cofactors contain various α-axial ligands, including 5,6-dimethylbenzimidazole (DMB) or adenine. The bacterium Salmonella enterica produces the corrin ring only under anaerobic conditions, but it can form "complete" corrinoids aerobically by importing an "incomplete" corrinoid, such as cobinamide (Cbi), and adding appropriate α- and ²-axial ligands. Under aerobic conditions, S. enterica performs the corrinoid-dependent degradation of ethanolamine if given vitamin B12, but it can make B12 from exogenous Cbi only if DMB is also provided. Mutants isolated for their ability to degrade ethanolamine without added DMB converted Cbi to pseudo-B12 cofactors (having adenine as an α-axial ligand). The mutations cause an increase in the level of free adenine and install adenine (instead of DMB) as an α-ligand. When DMB is provided to these mutants, synthesis of pseudo-B12 cofactors ceases and B12 cofactors are produced, suggesting that DMB regulates production or incorporation of free adenine as an α-ligand. Wild-type cells make pseudo-B12 cofactors during aerobic growth on propanediol plus Cbi and can use pseudo-vitamin B12 for all of their corrinoid-dependent enzymes. Synthesis of coenzyme pseudo-B12 cofactors requires the same enzymes (CobT, CobU, CobS, and CobC) that install DMB in the formation of coenzyme B12. Models are described for the mechanism and control of α-axial ligand installation. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate changes in the retinal microvasculature of young adults over 24 hours using optical coherence tomography angiography (OCT-A)., Methods: Participants (n = 44, mean age 23.2 ± 4.1 years, 24 myopes and 20 nonmyopes) with normal ophthalmological findings were recruited. Two macular OCT-A and OCT scans, systemic blood pressure, intraocular pressure (IOP), and biometry measurements were taken every four hours over 24 hours. Superficial and deep retinal layer en face images were analyzed to extract magnification-corrected vascular indexes using image analysis including foveal avascular zone metrics, vessel density, and perfusion density for the foveal, parafoveal, and perifoveal zones., Results: Significant diurnal variations (P < 0.001) were observed in the vessel and perfusion density in the three superficial retinal layer regions, with acrophase between 4:30 PM and 8:30 PM. Only foveal and parafoveal regions of the deep retinal layer exhibited significant diurnal variations with acrophase between 9 AM and 3 PM. Myopes and nonmyopes had different acrophases but not amplitudes in the parafoveal perfusion density of superficial retinal layer (P = 0.039). Significant correlations were observed between diurnal amplitudes or acrophases of superficial retinal layer indexes and systemic pulse pressure, IOP, axial length and retinal thickness., Conclusions: This study shows, for the first time, that significant diurnal variation exists in OCT-A indexes of macular superficial and deep retinal layer over 24 hours and were related to variations in various ocular and systemic measurements. Myopes and nonmyopes showed differences in the timing but not in amplitude of the superficial retinal layer parafoveal perfusion density variations but not in deep retinal layer.

Purpose: To investigate the effects of computer monitor pixel density on Landolt C visual acuity measurements and to provide appropriate pixel density recommendations for Landolt C vision chart design., Methods: Participants were 10 healthy observers aged 18-31 years (mean 21.7 ± 3.6). Logarithmic progression charts were used, consisting of eight rows of five Landolt C optotypes ranging from -0.40 logMAR to 0.30 logMAR. Monitor pixel angular subtense varied from 0.10 min arc to 1.97 min arc, achieved by changing the chart test distance. Testing took place with two filtering conditions: unfiltered optotypes, (pixels rendered either black or white) and anti-aliased optotypes with pixel luminance averaged for a pixel square and rendered as grey levels., Results: Each participant's acuity versus pixel size data sets were fitted by a nonlinear relationship with acuity equal to an asymptotic threshold visual acuity (VA as ) for small pixel sizes below a critical pixel size (P crit ). For pixel sizes larger than P crit  there was a linear relationship between acuity thresholds and pixel size. For anti-aliased Landolt Cs, mean P crit  was 1.23 min, and for unfiltered Landolt Cs average P crit was 0.65 min. For anti-aliased LandoltCs, P crit  was 2.01xVA as , and for unfiltered Landolt Cs P crit  was 1.05xVA as ., Conclusion: These results are quantitatively very similar to previous research on pixellation and Sloan optotype acuity. We have demonstrated that spatially filtering Landolt C optotypes acts as anti-aliasing, to make them more robust to the degradation effects of pixellation. Previous recommendations for maximum pixel size on Sloan letter vision charts can be applied safely to Landolt C charts., (© 2021 The Authors Ophthalmic and Physiological Optics © 2021 The College of Optometrists.)

Purpose: This article aims to illustrate the principles of bearing fixing, a new computer-controlled procedure for subjective determination of astigmatism, and to compare it with conventional clinician-controlled Jackson crossed-cylinder refraction., Methods: The principles and method for bearing fixing are described. Astigmatism was measured using bearing fixing and Jackson cross-cylinder twice on 20 visually normal participants aged between 18 and 34 years. After final sphere adjustment, acuity measurements were made with each refraction estimate., Results: Bearing fixing results could be obtained for all participants. Mean bearing fixing cylinder magnitude was slightly higher than Jackson cross-cylinder measures of cylinder magnitude, by 0.05D. Using vector analysis to take into account cylinder power and axis, mean bearing fixing astigmatism was not significantly different from cross-cylinder astigmatism, but did have higher test-retest variability (p < 0.05). Acuity with bearing fixing and cross-cylinder corrections did not significantly differ in average value or repeatability., Conclusions: Bearing fixing is a feasible method for subjective determination of astigmatism, and there are a number of potential improvements to the method which could make it faster and more precise., (© 2021 The Authors Ophthalmic and Physiological Optics © 2021 The College of Optometrists.)

Purpose: To assess the effect of changing anterior eye refractive power with contact lenses on the transverse magnification of en face images and associated vascular indices from optical coherence tomographic angiography (OCT-A)., Design: Prospective crossover study., Methods: Spherical soft contact lenses (-6 diopter [D] to +6 D in 2 D steps) were used to induce anterior eye refractive power changes in 11 healthy young adults and 3 × 3-mm macular scans were captured using OCT-A (Zeiss AngioPlex, software version 11.0; Cirrus HD-OCT 5000, Carl Zeiss Meditec Inc). Image transverse magnification was predicted based on refraction and biometry measurements and compared with empirical changes in the en face images measured with image analysis. Linear regression analysis was performed to assess the relationship between induced refractive ametropia and foveal avascular zone (FAZ) area, perimeter, circularity, and vessel density and perfusion density., Results: The predicted transverse magnification was linearly related to induced refractive ametropia and to the empirical transverse magnification changes (average slope: 1.02, 95% CI: 0.90-1.34). All the OCT-A indices showed linear relationships with induced refractive ametropia (P < .05) with the 12 D tested range altering the indices by 7% to 12%. After correcting for transverse magnification, all OCT-A indices except FAZ area were linearly related to induced refractive ametropia (P < .05) and were reduced to 1% to 9%., Conclusions: This study is the first to show that induced refractive ametropia can affect OCT-A image magnification and indices. These changes are clinically important and need to be considered along with biometry effects when interpreting OCT-A indices. Transverse magnification changes can affect the ability of OCT-A to precisely measure linear dimensions of blood vessels., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Stand magnifiers are still one of the most commonly prescribed classes of low vision devices. Their performance can be difficult to understand because stand magnifiers usually do not give an image at infinity. This review summarises the methods of describing image enlargement for stand magnifiers, emphasising their relationship to equivalent viewing distance (EVD). This is done in terms of the underlying optical equations, and measurement methods, and methods of prescribing. In the past, methods of determining EVD have been somewhat indirect, requiring accurate measurement of lens power, and image position. The use of digital photography provides an alternative, more direct, simpler method of determining EVD, which can be accomplished in-office. This method is described and it is demonstrated how it gives comparable results to older methods with small, clinically non-meaningful differences, that may be due to differences in image distance reference planes. Describing the performance of stand magnifiers in terms of their dioptric power, or in terms of 'nominal magnification' or 'trade magnification', is imprecise and misleading. It is better to use indices such as equivalent viewing power and EVD, which take into account the magnifier dioptric power, the image position of the magnifier and the distance a patient is from the magnifier. While EVD is a useful index for prescribing stand magnifiers, manufacturers do not always provide sufficient technical details to determine EVD for their stand magnifiers, and available tables of EVDs are more than a decade old and are likely to need updating. Photographic comparison provides a method for determining EVD, and this method can also be applied to other low vision devices., (© 2019 Optometry Australia.)

Significance: Confidence intervals are still seldom reported for Bland-Altman 95% limits of agreement. When they are reported, 50% of articles use approximate methods and 50% use exact methods., Purpose: Bland-Altman limits of agreement can be unreliable estimates, especially for small sample sizes. However, authors seldom use confidence intervals for limits of agreement. This article reviews their use in Optometry and Vision Science., Methods: A keyword search for "Bland," "Altman," "Bland-Altman," "LoA," and "limits of agreement" was conducted on the Optometry and Vision Science website within a time range from January 2016 to December 2018., Results: Fifty articles were reported or were judged to use Bland-Altman analysis; sample sizes ranged from 3 to 2072. Eight of these article reported confidence limits for limits of agreement, four of which used exact methods and four used Bland and Altman's approximate method., Conclusions: Use of confidence intervals for limits of agreement has increased in Optometry and Vision Science but is far from universal. To assist researchers in calculating exact confidence limits for Bland-Altman limits of agreement, spreadsheets are included for performing the calculations and generating Bland-Altman plots with the confidence intervals included.

Purpose: To investigate ocular and systemic diurnal rhythms in emmetropic and myopic adults and examine relationships with light exposure., Methods: Adult subjects (n = 42, 22-41 years) underwent measurements every 4 hours for 24 hours, including blood pressure, heart rate, body temperature, intraocular pressure (IOP), ocular biometry, and optical coherence tomography imaging. Mean ocular perfusion pressure (MOPP) was calculated. Saliva was collected for melatonin and cortisol analysis. Acrophase and amplitude for each parameter were compared between refractive error groups. Subjects wore a light, sleep, and activity monitor for 1 week before measurements., Results: All parameters exhibited significant diurnal rhythm (ANOVA, P < 0.05 for all). Choroidal thickness peaked at 2.42 hours, with a diurnal variation of 25.8 ± 13.44 μm. Axial length peaked at 12.96 hours, with a variation of 35.71 ± 6.6 μm. Melatonin peaked at 3.19 hours during the dark period, while cortisol peaked after light onset at 8.86 hours. IOP peaked at 11.24 hours, with a variation of 4.92 ± 1.57 mm Hg, in antiphase with MOPP, which peaked at 22.02 hours. Amplitudes of daily variations were not correlated with light exposure, and rhythms were not significantly different between emmetropes and myopes, except for body temperature and MOPP., Conclusions: Diurnal variations in ocular and systemic parameters were observed in young adults; however, these variations were not associated with habitual light exposure. Emmetropic and myopic refractive error groups showed small but significant differences in body temperature and MOPP, while other ocular and systemic patterns were similar.

Purpose: The effects of image doubling on logarithmic progression chart visual acuity were investigated by simulating diplopia on a computer monitor., Methods: Ten participants (6M, 4F) aged 21-28 years (mean 22.4 ± 2.3) were assessed viewing with their left eye while wearing their best correction. Stimuli were eight rows of five Sloan letters, from 0.4 to -0.3 logMAR (6/15 to 6/3) arranged in logarithmic progression format, generated on an HD monitor. Stimuli were generated with different magnitudes of doubling, different directions of doubling, and different intensity ratios between the ghost image and main images., Results: When the ghost image had the same intensity as the main image, there was a significant effect of doubling magnitude on visual acuity, with the mean acuity being -0.11 logMAR (6/4.7) for no doubling. Acuity thresholds (logMAR) increased when doubling exceeded 1 min of arc, reaching a level of 0.12 logMAR (6/7.9) for doubling of 16 min of arc. There were no significant effects of orientation on acuity, nor were there significant orientation-doubling magnitude interaction effects of visual acuity. Image doubling magnitude level affected visual acuity differently for different ghost image intensities, with the highest acuity elevation occurring when ghost and main images were equal or nearly equal. For faint ghost image intensities (10% and 20%) image doubling did not significantly affect visual acuity., Conclusions: Image doubling will degrade visual acuity if doubling is greater than 1 min of arc, and ghost images are sufficiently intense. However, even with very obvious visually-disturbing image doubling, visual acuity remains only slightly reduced., (© 2019 The Authors Ophthalmic & Physiological Optics © 2019 The College of Optometrists.)

Significance: This is the first report of monocular ghost image offset thresholds measured using O optotypes. Monocular diplopia is a complaint of patients and is the result of a variety of etiologies. Furthermore, monocular image doubling also can be a confounding variable of vectographic stereoacuity tests, warranting an investigation of ghost image offset thresholds., Purpose: To measure ghost image offset thresholds of normal observers and how they are affected by offset orientation, target size, and ghost image relative luminance., Methods: Participants were five individuals without ocular abnormalities aged 21 to 32 years. Stimuli were viewed monocularly and consisted of Sloan "O" optotypes generated on a computer monitor with varying levels of image doubling. Ghost image offset thresholds were determined using a spatial 2-alternative forced-choice paradigm and probit analysis of the frequency of seeing data., Results: Under close-to-optimal conditions, monocular ghost image offset thresholds ranged between 14 and 22 arc seconds, a level that might be considered a hyperacuity. Ghost image offset detection thresholds demonstrated a U-shaped relationship with optotype size, with optimum thresholds occurring for optotypes sizes of approximately -0.15 logarithmic minimum angle of resolution. There was no measurable effect of offset orientation on ghost image offset detection thresholds. Monocular ghost image offset detection thresholds decreased as ghost image relative luminance increased., Conclusions: Ghost image offset detection thresholds can be quite low even when viewing under monocular conditions and relatively low ghost image relative luminance. This should be considered when designing and interpreting the results of vectographic stereoacuity tests.

Bland and Altman described approximate methods in 1986 and 1999 for calculating confidence limits for their 95% limits of agreement, approximations which assume large subject numbers. In this paper, these approximations are compared with exact confidence intervals calculated using two-sided tolerance intervals for a normal distribution. The approximations are compared in terms of the tolerance factors themselves but also in terms of the exact confidence limits and the exact limits of agreement coverage corresponding to the approximate confidence interval methods. Using similar methods the 50th percentile of the tolerance interval are compared with the k values of 1.96 and 2, which Bland and Altman used to define limits of agreements (i.e. [Formula: see text]+/- 1.96S d and [Formula: see text]+/- 2S d ). For limits of agreement outer confidence intervals, Bland and Altman's approximations are too permissive for sample sizes <40 (1999 approximation) and <76 (1986 approximation). For inner confidence limits the approximations are poorer, being permissive for sample sizes of <490 (1986 approximation) and all practical sample sizes (1999 approximation). Exact confidence intervals for 95% limits of agreements, based on two-sided tolerance factors, can be calculated easily based on tables and should be used in preference to the approximate methods, especially for small sample sizes.

Purpose: To assess the effects of changing computer monitor pixel density on visual acuity measurements made using Sloan optotypes., Methods: Acuity was measured on 10 participants aged 19 to 38 years (mean 27.9 ± 7.0) measured binocularly wearing their best spectacle correction. Stimuli were eight lines of five Sloan letter optotypes in logarithmic progression, ranging in size from -0.4 to 0.3 logMAR. Test distance was varied so that pixels on the monitor ranged in size from 0.125 mins of arc to 1.97 mins of arc. Two sampling approaches were used: (1) unfiltered sampling, with each pixel rendered either black or white; and (2) filtered sampling with pixel luminance averaged across a pixel aperture, giving grey-scale smoothing of letter edges., Results: A broken line fit was made to each data set, with acuity being stable at an asymptotic threshold VA as for small pixels sizes, with thresholds increasing linearly when pixel sizes exceeded a critical pixel size P crit . For unfiltered stimuli, P crit averaged 1.1 mins of arc and for unfiltered stimuli averaged 0.69 mins of arc. For filtered stimuli, P crit was 1.79xVA as , and for unfiltered P crit was 1.05xVA as ., Conclusion: The results show that grey-scale filtering makes acuity measurement more resistant to the effects of pixellation. Based on a conservative interpretation of these findings, we make the recommendation that charts be constructed with, for filtered optotypes, a maximum pixel size of 0.6 x of the smallest MAR used and, for unfiltered optotypes, 0.35 x the smallest MAR used., (© 2017 The Authors Ophthalmic & Physiological Optics © 2017 The College of Optometrists.)

Purpose: The Enright phenomenon describes the distortion in speed perception experienced by an observer looking sideways from a moving vehicle when viewing with interocular differences in retinal image brightness, usually induced by neutral density filters. We investigated whether the Enright phenomenon could be induced with monocular pupil dilation using tropicamide., Methods: We tested 17 visually normal young adults on a closed road driving circuit. Participants were asked to travel at Goal Speeds of 40km/h and 60km/h while looking sideways from the vehicle with: (i) both eyes with undilated pupils; (ii) both eyes with dilated pupils; (iii) with the leading eye only dilated; and (iv) the trailing eye only dilated. For each condition we recorded actual driving speed., Results: With the pupil of the leading eye dilated participants drove significantly faster (by an average of 3.8km/h) than with both eyes dilated (p=0.02); with the trailing eye dilated participants drove significantly slower (by an average of 3.2km/h) than with both eyes dilated (p<0.001). The speed, with the leading eye dilated, was faster by an average of 7km/h than with the trailing eye dilated (p<0.001). There was no significant difference between driving speeds when viewing with both eyes either dilated or undilated (p=0.322)., Conclusions: Our results are the first to show a measurable change in driving behaviour following monocular pupil dilation and support predictions based on the Enright phenomenon., (Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: To assess whether the slopes of psychometric functions for measuring low contrast letter acuity were different from those for measuring high contrast letter acuity., Methods: Ten participants, wearing their best spectacle correction, were assessed monocularly. Stimuli were logarithmic progression charts, generated on a computer monitor, with nine rows of five randomised Sloan letters generated in either high contrast format (Weber contrast 99.2%) or low contrast format (Weber contrast 18.7%). For each participant, psychometric functions were generated by probit analysis of the data on each of 16 attempts at a low contrast chart and 16 attempts at a high contrast chart. Each of these probit fits yielded an estimate of Probit Size which provided information about how steep or flat the psychometric function was, along with an estimate of Probit Acuity Threshold., Results: Probit Size was significantly larger (p < 0.001) for low contrast charts than for high contrast charts, indicating that psychometric functions were flatter for low contrast charts. Mean Probit Sizes in logMAR were 0.099 (SEM 0.022) for low contrast charts and 0.071 (SEM 0.009) for high contrast charts if a guess rate of 1/26 was assumed, or were 0.086 (SEM 0.019) for low contrast charts and 0.064 for high contrast charts if a guess rate of 1/10 was assumed. Monte Carlo analysis showed that these means were likely to be biased estimates, with true Probit Size probably being larger (i.e. slightly flatter fits) by 0.016-0.019 logMAR. As expected, Probit Acuity Thresholds were poorer for low contrast charts than for high contrast charts (p < 0.001)., Conclusion: Our Monte Carlo modelling showed that such differences in acuity psychometric functions would be expected to give greater intra-subject variability in low contrast letter-by-letter acuity thresholds than for high contrast letter-by-letter acuity thresholds, and that this difference would depend on the termination rule used when measuring acuity. Likewise the variation in letter-by- letter acuity thresholds with termination rule will be different for high and low contrast charts. For low contrast and high contrast Sloan letter charts in a standard logarithmic format, a termination rule of four mistakes on a row, will give close to optimum sensitivity-to-change., (© 2017 The Authors Ophthalmic & Physiological Optics © 2017 The College of Optometrists.)

Purpose: The previous literature on Bland-Altman analysis only describes approximate methods for calculating confidence intervals for 95% limits of agreement (LoAs). This article describes exact methods for calculating such confidence intervals based on the assumption that differences in measurement pairs are normally distributed., Methods: Two basic situations are considered for calculating LoA confidence intervals: the first, where LoAs are considered individually (i.e., using one-sided tolerance factors for a normal distribution); and the second, where LoAs are considered as a pair (i.e., using two-sided tolerance factors for a normal distribution). Equations underlying the calculation of exact confidence limits are briefly outlined., Results: To assist in determining confidence intervals for LoAs (considered individually and as a pair), tables of coefficients have been included for degrees of freedom between 1 and 1000. Numerical examples, showing the use of the tables for calculating confidence limits for Bland-Altman LoAs, have been provided., Conclusions: Exact confidence intervals for LoAs can differ considerably from the Bland and Altman approximate method, especially for sample sizes that are not large. There are better, more precise methods for calculating confidence intervals for LoAs than the Bland and Altman approximate method, although even an approximate calculation of confidence intervals for LoAs is likely to be better than none at all. Reporting confidence limits for LoAs considered as a pair is appropriate for most situations; however, there may be circumstances where it is appropriate to report confidence limits for LoAs considered individually.

Although comparison phakometry has been used by a number of studies to measure posterior corneal shape, these studies have not calculated the size of the posterior corneal zones of reflection they assessed. This paper develops paraxial equations for calculating posterior corneal zones of reflection, based on standard keratometry equations and equivalent mirror theory. For targets used in previous studies, posterior corneal reflection zone sizes were calculated using paraxial equations and using exact ray tracing, assuming spherical and aspheric corneal surfaces. Paraxial methods and exact ray tracing methods give similar estimates for reflection zone sizes less than 2 mm, but for larger zone sizes ray tracing methods should be used.

Purpose: Lid architecture, lid tension, blink action, and blink rate may all influence rigid lens centration and stability. The aims of this study were to assess the nature of the relationship between lid geometry and lens position and to examine the influence of lens-lid interactions on the association between lens position and lens center of gravity and mass., Methods: Eight subjects (four with high riding lenses and four with low riding lenses) participated in the study. Each subject was fit with 12 lenses-six designs in each of two materials. Lens center of gravity was calculated and lens mass was measured in every case. For each lens, the following four lens dynamics variables were assessed over a five blink cycle for both the vertical and horizontal meridians: 1) initial lens position; 2) settled lens position; 3) amount of lens movement; and 4) rate of lens movement. Lower lid position and palpebral aperture height were measured for each subject., Results: Graphical analysis showed that a low upper lid position and small palpebral aperture promoted superior lens decentration, while a high upper lid position and wide palpebral aperature predisposed an individual to inferior lens decentration. Significant lid-lens overlap was a common finding with high riding lenses in both the initial and settled lens positions. The results also suggested that while a rigid lens tended to become more stable as the lens center of gravity shifted further behind the corneal apex, this gravitational effect was reduced for lenses that interacted with the upper lid., Conclusions: Lid geometry can influence rigid lens centration and stability by modifying the effects of lens design and lens mass. We recommend that consideration be given to the nature of potential lens-lid interactions prior to lens fitting.

Purpose: Center of gravity and lens mass have both been shown to influence rigid lens centration and stability. The purpose of this study was to investigate the relative contributions of these two factors to rigid lens dynamics., Methods: Eight subjects (four with high-riding lenses and four with low-riding lenses) participated in the study. Each subject was fit with 12 lenses-six designs in each of two materials. Center of gravity and lens mass were recorded in every case. For each lens, four lens dynamics variables were assessed over a five-blink cycle for both the vertical and the horizontal meridians: 1) initial lens position; 2) settled lens position; 3) amount of lens movement; and 4) rate of lens movement., Results: Multiple regression and correlation analysis showed that center of gravity influences initial and settled lens position, in both the horizontal and the vertical meridians. Mass alone was found not to be a significant predictor of rigid lens dynamics. The effect of center of gravity on settled vertical lens position was only apparent when high rider and low rider subgroups were analyzed separately, with a posterior movement of the center of gravity being associated with a lowering of the settled lens position for high rider subjects, and a raising of the settled lens position for low rider subjects. The results suggest that a rigid lens will become more stable as the center of gravity is shifted further behind the lens vertex, but this effect is reduced as lens mass is increased., Conclusions: The location of the center of gravity of a rigid lens influences its on-eye centration and stability more so than does lens mass.